Synthesis of Quinazoline-2,4,5,8(1H,3H)-tetrones and Their Amine Nucleophilic Addition Chemistry

Article abstract of DOI:10.1021/jo00224a042

The amination of qyinazoline-2,4,5,8(1H,3H)-tetrones was studied in conjunction with synthetic efforts toward the imidazo<4,5-g>quinazoline-4,6,8,9-tetrone system.Under the basic reaction conditions employed, the quinazolinetetrone system possesses a negative charge delocalized into both the pyrimidine and benzoquinone rings.Thus, unfavorable electrostatic effects preclude nucleophilic addition to this system by amines.Activation toward nucleophilic attack was realized by the placement of a 6-acetamido group (1).Even though this system is still anionic under the amination conditions, substitution products were observed under mild conditions.Thus, treatment of 1 with aniline/DMF resulted in the formation of the 8-phenylimino derivative (11) while treatment with methylamine (in water or DMF) resulted in formation of the 6-methylamino 8-methylimino derivative (3).The activating influence of the 6-acetamido group is proposed to involve the contribution of tautomeric species such as 1a^-.Nucleophilic attack at either the 8- or 6-position of 1a^- is electrostatically favorable since the negative charge develops at the acetamido oxygen which is removed from the anionic quinazoline nucleus.